The present invention relates to compositions useful for the delivery, and preferably the oral delivery, of antigens and adjuvants to animals. Methods for the preparation and for the administration of these compositions are also disclosed.
Conventional means for delivering antigens to their intended targets are often severely limited by the presence of biological, chemical, and physical barriers. Typically, these barriers are imposed by the environment through which delivery must take place, the environment of the target for delivery, or the target itself.
Oral delivery of antigens would be the route of choice for administration to animals if not for physical barriers such as the mucous layer and the epithelial cells of the gastrointestinal (GI) tract. Oral delivery is also impeded by chemical barriers such as the pH in the GI tract and the presence in the oral cavity and the GI tract of powerful digestive enzymes. Furthermore, orally administered soluble and insoluble antigens can induce a non-responsive state or tolerance.
Methods for orally administering antigens have been developed which rely on the use of either attenuated microorganisms or polylactide/polyglycocide (PLA/PGA) microspheres to increase antigen presentation to and uptake by the appropriate antigen presenting cells. Attenuated organisms, unless properly delivered, can regain virulence, however. Additionally, broad spectrum use of PLA/PGA microspheres is not possible because these carriers require organic solvents that may alter or denature antigens. Furthermore, PLA/PGA systems are difficult to manufacture.
More recently, microspheres comprising artificial polymers of mixed amino acids (proteinoids) have been described for delivering biologically active agents including antigens. Santiago, et al. Pharmaceutical Res. Vol. 10, No. 8, (1993).
Adjuvants have been coadministered with antigens to increase the effectiveness of antigens, but adjuvants and antigen/adjuvant compositions are susceptible to the common problems of oral delivery described above.
Consequently, there is still a need in the art for simple, inexpensive, and easily prepared systems which can effectively deliver a broad range of antigens, particularly via the oral route.
The present invention provides compositions for delivering antigens. These compositions are suitable for delivery via the oral route and comprise:
(a) an antigen;
(b) an adjuvant; and
(c) at least one carrier comprising a member selected from the group consisting of;
(i) an acylated amino acid or a salt thereof;
(ii) a polyamino acid comprising at least one acylated amino acid or a salt thereof;
(iii) a sulfonated amino acid or a salt thereof;
(iv) a polyamino acid comprising at least one sulfonated amino acid or a salt thereof; or
(v) any combination thereof.
These compositions can be orally administered to animals to produce or prime and/or to boost an immunogenic response and to achieve immunization. When these compositions are used to boost immunogenic responses the prime can be delivered by the compositions of the present invention or other compositions.
Also contemplated are methods for preparing mixtures of microspheres of an antigen, an adjuvant, and a carrier as described above, and optionally, a dosing vehicle.